C-150 a Mannich-type curcumin derivative, exhibited pronounced cytotoxic effects against
eight glioma cell lines at micromolar concentrations. Inhibition of cell proliferation
by C-150 was mediated by affecting multiple targets as confirmed at transcription
and protein level. C-150 effectively reduced the transcription activation of NFkB,
inhibited PKC-alpha which are constitutively over-expressed in glioblastoma. The effects
of C-150 on the Akt/ Notch signaling were also demonstrated in a Drosophila tumorigenesis
model. C-150 reduced the number of tumors in Drosophila with similar efficacy to mitoxantrone.
In an in vivo orthotopic glioma model, C-150 significantly increased the median survival
of treated nude rats compared to control animals. The multi-target action of C-150,
and its preliminary in vivo efficacy would render this curcumin analogue as a potent
clinical candidate against glioblastoma.
